DESCRIPTION (Unedited Applicant's Abstract): Gram-negative bacilli (GNB) are pathogens that are capable of causing severe, life-threatening pneumonia. More than 60 percent of nosocomial pneumonias are caused by GNB and associated mortality rates are often >50 percent. Over the last 10-15 years, there has been little improvement in outcome from this infection. As a result, this syndrome continues to cause significant morbidity and mortality and strongly contributes to the economic burden of our national health care system. The successful use of immune intervention in the treatment or modulation of infections has marked the beginning of a new era in the management of infectious diseases. There exists a delicate balance between an efficacious and injurious host defense response. An understanding of the host response in GNB pneumonia and how bacterial components affect this response will, in turn, lead to the development of rapid diagnostic tests that will enable the clinician to effectively utilize a variety of biologic modulators. It is also necessary to understand the relative role of bacterial components versus host factors in mediating damage to the lungs prior to therapeutic manipulations on which little is known. This information will enable us to appreciate the relative risk benefit ratio of altering the host response. Further, a more precise clarification of which host components are damaged is also needed. This knowledge may identify independent therapeutic interventions. Their global hypothesis is that surface components of GNB and/or secreted proteins differentially alter host antibacterial defenses and directly, and/or indirectly (by inflammatory mechanisms) promote lung injury. Preliminary data supports this hypothesis. These responses will have significant implications when attempting therapeutic immune interventions. The goals of this proposal are to determine the mechanisms by which the bacterial capsule and 0-specific antigen modulate neutrophil recruitment into the lungs in a diametrical manner and extend our evaluations on the relative roles of bacterial factors (e.g. hemolysin) and bacterially induced host response elements in directly mediating the pathogenesis of lung injury.